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Published on: October 27, 2014
Wilms' tumor protein Wt1 regulates the Interleukin-10 (IL-10) gene
Lina K Sciesielski1, Karin M Kirschner, Holger Scholz
1Charité-Universitaetsmedizin Berlin, Institut fuer Vegetative Physiologie, Hessische Straße 3-4, 10115 Berlin, Germany.
Abstract:
We identified the Wilms' tumor protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.
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